NSUN3-mediated m5C modification of FABP5 regulates lipid droplets through autophagy to alleviate osteoarthritis progression

Lipid droplets (LDs) are closely associated with the onset and progression of osteoarthritis (OA). RNA 5-Methylcytosine (m5C) modification plays a key role in various diseases, but its role in the pathogenesis of OA is largely unknown. In this study, NSUN3 expression was the most significantly down-regulated methyltransferase of the NSUN family in OA. Overexpression of NSUN3 alleviated OA by promoting autophagy to clear abnormal lipid accumulation in chondrocytes, whereas siNSUN3 had the opposite effect. Mechanistically, NSUN3 mediated m5C modification of FABP5 mRNA and enhanced its mRNA stability. Intra-articular injection of AAV-NSUN3 attenuated OA in rats. Overall, NSUN3 might be a potential therapeutic target for OA and even for dysregulated LDs in a wide range of diseases.